1. Field of the Invention
This invention relates to a method and apparatus for assessing vascular endothelial function.
2. Description of the Related Art
Vascular endothelium is a cell group that constitute a layer of lining blood vessels, functioning not only to line the inner wall of blood vessels and separate blood components from body tissues but also to produce or release substances which control the biological characteristics of blood vessels including dimension, elasticity, permeability and reactivity. Since impairment of vascular endothelial function is found in earlier stages of arteriosclerosis where arteriosclerosis has not yet developed or clinically manifested, it is possible to prevent the development or treat the arteriosclerosis earlier by detecting the impairment of vascular endothelial function.
A non-invasive method for assessing flow-mediated dilation induced by reactive hyperemia by using an ultrasonic device is known as a method for assessing vascular endothelial function (for example, as shown in the non-patent literature 1). The above reactive hyperemia is a transient increase in organ blood flow that takes place following a brief period of ischemia (arterial occlusion) and subsequent release. The flow-mediated dilation is a reaction in which an increased arterial blood flow stimulates vascular endothelium of the artery concerned, thus secreting from vascular endothelium endothelium-derived relaxing factors (EDRF; nitrogen monoxide and analogous substances), which are substances to dilate blood vessels, resulting in an increase in the diameter of the artery concerned. As a result, since endothelium-derived relaxing factors are secreted at a smaller quantity when the vascular endothelial function is impaired, the diameter of the artery will not increase as expected even after an increase in arterial blood flow caused by the reactive hyperemia. Thus, vascular endothelial function can be assessed by referring to the extent of the increase in diameter of the artery with the peripheral reactive hyperemia.
In the method described in the non-patent literature 1, an ultrasonic probe was used to provide consecutive images of an artery by which a maximum increase rate of the arterial diameter after release from ischemia in relation to that before the ischemia was calculated to assess vascular endothelial function based on the maximum increase rate. The above maximum increase rate is called % FMD (flow mediated dilatation), which is about 10% for healthy adults. 3 to 4% FMD is indicative of endothelial dysfunction and likely that arteries in major organs have already been atherosclerotic or may have an increased risk for arteriosclerosis.
Methods for inducing release of endothelium-derived relaxing factors from vascular endothelium include methods for causing the above hyperemic reaction or increased blood flow and for injecting into an artery substances stimulating the release of EDRF such as acetylcholine.
[Non-patent Literature 1]
Page 104 to 106, “Pulse Wave Velocity,” First edition compiled by Toshio Ozawa and Yoshiaki Masuda, Published by Medical Review Co., Ltd. May 1, 2002
However, the following problems are found in the method for calculating % FMD by referring to the vasodilation response assessed by an ultrasonic device. First, a major problem with the method is the large variation in results, as high as 2 to 3%, among examiners and laboratories. Since the % FMD is considered normal at about 10% and abnormal at 3 to 4%, a variation of as high as 2 to 3% poses a serious problem. The great variation is due to the need for skill in detecting correct signals such as placing an ultrasonic probe vertically to a vessel, and variation in the point of time in determining a diameter of the vessel because it is necessary to detect from consecutive images of a pulsating blood vessel the timing when the greatest dilation of the vessel takes place after release from ischemia, and also to determine a diameter of the blood vessel at the end of diastolic phase of the heart. Therefore, it may take several months to acquire this skill, and it is reported that % FMD is not reliable unless the result is obtained from an examiner with substantial experience (for example, about six-months). Second, this method has an inevitable theoretical limitation. The arterial diameter shows not only pulsation but also spontaneous variations. The arterial diameter is dependent on heart rate and blood pressure, both of which show, even in a short term, physiological fluctuation such as those relating respiration and Mayer wave (10-second rhythm). Also, neurohumoral, thermoregulatory and emotional factors (which could accompany arterial occlusion) affect the vascular tone directly and indirectly through heart rate and blood pressure. The influences of these systemic factors confound the assessment of endothelium-dependent vascular responses and partly contribute to the large variation of % FMD. Finally, in case of the brachial artery, the diameter of blood vessel is about 5 mm and expected change of the diameter would be less than 0.5 mm, or dilation corresponding to less than 10% of a diameter of the vessel. Thus, such exact detection requires a high-performance and highly priced ultrasonic device, which is another problem.